In view of the uneven settlement of ballasted track subgrade, the overall deformation analysis of ballasted track structure is carried out. Based on the coupling method of discrete element method and multi-flexible body dynamic (DEM-MFBD), a simplified 2.5-dimension coupling model of ballasted track is introduced and applied to the study of meso-mechanical properties of ballasted track. Based on the characteristics of the coupling model, the load and stiffness reduction method is proposed. The overall stress and deformation of the ballast track structure under different subgrade settlement wavelengths and amplitudes are calculated and analyzed. At the same time, its influence of uneven subgrade settlement on unsupported sleepers is studied. The results show that the increase of subgrade settlement amplitude or wavelength obviously leads to the increase of track irregularity and the outward expansion of the stress concentration position of the ballast bed. The ratio of rail settlement area to subgrade settlement area (S1/S0) can reflect the situation of unsupported sleepers. It is found that the unsupported sleepers are caused when the subgrade settlement amplitude is 10mm ~ 15mm. Therefore, it is suggested that the subgrade settlement amplitude should be controlled within 10mm, so that the engineering department can control the diseases such as unsupported sleepers and track irregularity.